PROJECT SUMMARY/ABSTRACT Hypertension is a risk factor for chronic kidney disease (CKD) progression but only 77% of adolescents with CKD are adherent to antihypertensive medications despite evidence that adherence slows disease progression. Mobile health (mHealth) applications show promise for improving adherence but most are not designed within health-promotion frameworks, only send medication reminders, use unreliable outcome measures, and/or have small effects on adherence. Nonadherence is a public health problem that may benefit from using health communication strategies to advance beyond reminders and improve mHealth efficacy. Highly effective health messages modify perceptions, attitudes, and skills to facilitate behavioral change; inappropriately framed messages (e.g., use of fear appeals) may have unintended, negative effects on health behaviors (i.e., reduce adherence). For adolescents with CKD, framing mHealth messages to motivate sustained adherence may be a key factor in preventing disease progression; however, there has been little empirical study to guide the use of this approach. The COM-B model states that capability, opportunity, and motivation interactively modify health behaviors, including adherence. Our preliminary data with 128 adolescents with CKD showed that motivation and capability to adhere are associated with antihypertensive medication adherence. mHealth reminders can be conceptualized as adherence opportunities. To disseminate more efficacious mHealth messages, formative research is needed. Hence, we propose (1) formulating mHealth messages to incorporate effective framing strategies and to target capability, opportunity, and motivation to adhere through an iterative process and preliminarily evaluating the messages with adolescents with CKD (N=10) and pediatric nephrologists (N=7), (2) using a pilot randomized controlled trial (RCT) with adolescents with CKD (ages 11-21 years; N=40) to evaluate our COM-B message intervention versus an active control group that only receives medication reminders through an existing mHealth application, and (3) qualitatively assessing adolescents' experiences with our COM-B messages in post-study interviews (N=20) to refine messages for an efficacy trial. We expect that our COM-B messages will be rated as efficacious, acceptable, appropriate, and understandable by ?85% of adolescents and pediatric nephrologists, the intervention group will have higher post-randomization adherence and capability and motivation to adhere than the active control group, and, <10% of adolescents in the intervention group will report that the messages reduced their desire to take their medication. Exploratory time series analyses will investigate whether the intervention group exhibits a faster rate of improvement in adherence post-randomization compared to the active control group. Results of this study may improve our ability to efficaciously frame mHealth messages that facilitate long-term improvements in medication adherence for adolescents with CKD and, potentially, children with other chronic illnesses requiring daily medications. If our messaging intervention has greater effects on adherence than the active control condition, a fully-powered efficacy trial would be warranted.